Parrella Paola, Barbano Raffaela, Pasculli Barbara, Fontana Andrea, Copetti Massimiliano, Valori Vanna Maria, Poeta Maria Luana, Perrone Giuseppe, Righi Daniela, Castelvetere Marina, Coco Michelina, Balsamo Teresa, Morritti Maria, Pellegrini Fabio, Onetti-Muda Andrea, Maiello Evaristo, Murgo Roberto, Fazio Vito Michele
Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013 San Giovanni Rotondo, (FG), Italy.
Mol Cancer. 2014 Jun 4;13:142. doi: 10.1186/1476-4598-13-142.
MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types.
We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n = 150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed.
The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n = 11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n = 90, Median 0.09; IQR 0.04-0.29) (p = 0.028). In the subgroup of patients without synchronous metastases (n = 90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 1.16, p = 0.021 and HR 1.20, p = 0.015 respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable (HR1.30, p < 0.001, and HR 1.31, p = 0.003 respectively for 0.10 unitary increase of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p = 0.009) for OS and from 0.735 to 0.767 (p = 0.050) for DFS.
Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.
微小RNA-10b（miR-10b）通过靶向HOXD10转录抑制因子在调节肿瘤侵袭和转移中发挥重要作用，并且已发现在几种肿瘤类型中其表达上调。
我们评估了根据REMARK指南纳入的、具有至少36个月随访的乳腺癌患者前瞻性队列中配对的肿瘤和正常标本中miR-10b的表达（n = 150）。测量了RNA质量，仅分析RNA完整性数值（RIN）≥7.0的样本。
通过RT-qPCR测定肿瘤中miR-10b与其正常对应物相比的相对表达（RER）。与无转移患者（n = 90，中位数0.09；四分位间距0.04 - 0.29）相比，有同步转移患者亚组（n = 11，中位数0.25；四分位间距0.11 - 1.02）的miR-10b RER更高（p = 0.028）。在无同步转移患者亚组（n = 90）中，较高的miR-10b RER与疾病进展和死亡风险增加相关，在单变量（miR-10b RER水平每增加0.10单位，HR分别为1.16，p = 0.021和HR 1.20，p = 0.015）和多变量（miR-10b RER水平每增加0.10单位，HR分别为1.30，p < 0.001和HR 1.31，p = 0.003）Cox回归模型中均如此。将miR-10b RER添加到诺丁汉预后指数（NPI）中可提高对36个月临床结局的鉴别能力和风险重新分类能力。总生存期（OS）的生存C指数从0.849显著增加到0.889（p = 0.009），无病生存期（DFS）从0.735增加到0.767（p = 0.050）。
我们的结果提供了证据，表明将miR-10b RER添加到临床常规使用的预后因素中可提高对乳腺癌患者总体死亡率和疾病进展的预测能力。
